Preparation Of High-purity Heparin And Dertamn Sulfate By Anion-exchange Chromatography

Heparin sodium and dermatan sulfate (DS) are both glycosaminoglycans, they arebiological active and have a wide range of applications in medicine. Heparin sodium ismainly applied in clinical cardiovascular disease prevention and treatment, and as ananticoagulant and antithrombotic drug. Heparin is currently the most principal clinicalapplied anticoagulant, while DS can be used in treatment of osteparthropathy andhypertension disease. Since large quantities of DS was usually produced as byproductsduring heparin industrial production from pig intestine, the purpose of this thesis is tryingto optimize the current production process in order to acquire high-purity heparin andhigh-purity DS.(1) Heparin and DS detection and analysis methods established in our laboratory,including heparin and DS purity measured by strong-anion-exchange-HPLC (SAX-HPLC)and cellulose acetate membrane electrophoresis, molecular weight determination by highperformance size exclusion chromatography combined with a triple detector array(TDA-SEC).(2) Research about the influence of the two factors-the temperature and pH value onresin adsorption efficiency of heparin. No significant effect of temperature on resinadsorption showed, but it’s found pH8.2is the best pH for resin adsorption efficiency andspeed.(3) Optimization of conventional anion-exchange chromatography process in order toachieve high purity Heparin and high-purity DS production. Firstly, duality gradientelution concentration ranges was confirmed by linear gradient elution, then through theoptimization of multiple chromatography, the elution concentration.1.15mol/L and2mol/L was selected, and the purify of DS and heparin were rewned to88%and96.6%respectively.